Antitranspirant Deodorant Cosmetic Composition Having Dermo-Calming Action

Description

FIELD OF THE INVENTION

The present invention relates to antiperspirant deodorant cosmetic compositions with dermo-calming action for after-depilation sensitized skin, applicable in the cosmetic, hygiene and personal-care industry.

BACKGROUND OF THE INVENTION

Deodorants are intended for perfuming the body and, in general, they contain antimicrobial components, particularly antibacterial and antifungal, which eliminate bacteria and fungi that cause bad smell on the skin. Deodorants may be applied to armpits to perfume them and diminish the odors generated in this body region; however they do not prevent perspiration.

Antiperspirants have the function of controlling the perspiration by inhibiting or reducing it, thus guaranteeing protection against sweat, besides having antimicrobial action, eliminating the microorganisms that cause bad smell. The antiperspirant action is due to the fact that this product acts by forming a blocking film that prevent sweat from coming out, without causing damage to one's health.

It is known that depilation, be it by wax, laser or nippers, induces cutaneous irritation in determined persons and body regions.

Among the measures which one should take with depilation are: non-exposure to direct sunshine, skin cleaning, use of light and loose clothes, as well as attention to deodorants, creams and body oils used after the depilatory procedure. For this reason, care with the skin has become essential, although cutaneous irritations still occur, even with such care.

In this regard, the search for specific products for this purpose, particularly for deodorants that provide relief of irritation caused on the skin, i.e., sensitized by depilation, becomes critical. Also, in addition to deodorants that relieve irritation, it becomes essential to develop products that group deodorant characteristics to fight odor, antiperspirant for reducing sweat, and still that have a dermo-calming action on the skin.

A few examples of prior-art documents related to the area of the present invention, particularly antiperspirant deodorants, are presented hereinafter.

Patent application PI0924661-4, published on Nov. 21, 2012, in the name of Symrise AG, relates to ω-cycle-hexylalkan-1-ols, to the use of said compounds as antimicrobial agents for the treatment of odor on the body or for the preparation of an antimicrobial cosmetic or pharmaceutical formulation. Said PI0924661-4 further describes antimicrobial formulations containing, for instance, 2-methyl-cyclohexylpentanol. However, said document does not mention or suggest the use of said active or formulations thereof as antiperspirant deodorants with dermo-calming action, especially for after-depilation sensitized skin.

U.S. Pat. No. 8,115,033, published on Feb. 14, 2012, in the name of Symrise Ag relates to the chemical compound 3-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)-1-propanone, which is different from the chemical compound of the present invention called SymDeo® B125: 2-methyl-5-cyclohexylpentanol. In the same way as the above-cited document, U.S. Pat. No. 8,115,033 does not mention or suggest the use of the active presently described and claimed or its formulations as antiperspirant deodorants with dermo-calming action, or use on after-depilation sensitized skin. In addition, even if this were the case, this is an active ingredient that is not foreseen in the composition of the present invention.

U.S. Pat. No. 6,172,016, published on Jan. 9, 2001, in the name of Bush Boakes Allen Inc., is directed to the use of pentane derivatives as cosmetic ingredients. The difference with respect to the chemical compounds SymDeo of the present invention lies in the carbon to which the methyl radical is attached, which is the third one in the American patent, namely: 3-methyl-5-cyclohexylpentanol. Again, this is a document that foresees a deodorant composition without the after-depilation calming benefit for sensitized skins.

Therefore, the need to develop antiperspirant deodorant formulations with dermo-calming action still remains, particularly for sensitized skins, which, in addition to the deodorant and antiperspirant properties, will exhibit emollient sensorial characteristics and a protective film, and provide dermo-calming action on the skin. Such need is fully met with the composition of the present invention.

SUMMARY OF THE INVENTION

The present invention relates to antiperspirant deodorant cosmetic compositions with dermo-calming action, which comprise as active ingredients, 2-methyl-5-cyclohexylpentanol and aluminum hydrochloride, as well as commercially acceptable adjuvants, directed to application in the cosmetic, hygiene and body-care industry.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 refers to the result of treatment average as a function of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-03) versus control composition on erythema induced by the tape-stripping technique.

FIG. 2 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition of the present invention (called 13-39540-03) versus control composition on erythema induced by the tape stripping technique.

FIG. 3 refers to the result of the average difference as a function of the time T0 of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-03) versus control composition on erythema induced by the tape-stripping technique.

FIG. 4 refers to the result of treatment average as a function of the time of the test for instrumental evaluation of the effect of the composition of the present invention (called 13-39540-04) versus control composition on erythema induced by the tape-stripping technique.

FIG. 5 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-04) versus control composition on erythema induced by the tape-stripping technique.

FIG. 6 refers to the result of average difference as a function of the time T0 of the test for instrumental evaluation of the effect of the composition of the invention (called 13039540-04) versus control composition on erythema induced by the tape-stripping technique.

FIG. 7 refers to the result of treatment average as a function of the time of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-01) versus control composition on erythema induced by the tape-stripping technique.

FIG. 8 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-01) versus control composition on erythema induced by the tape-stripping technique.

FIG. 9 refers to the result of average difference as a function of the time T0 of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-01) versus control composition on erythema induced by the tape-stripping technique.

FIG. 10 refers to the result of treatment average as a function of the time of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-02) versus control composition on erythema induced by the tape-stripping technique.

FIG. 11 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-02) versus control composition on erythema induced by the tape-stripping technique.

FIG. 12 refers to the result of average difference as a function of the time T0 of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-02) versus control composition on erythema induced by the tape-stripping technique.

FIG. 13 refers to the average value of the erythema (E) for the product and control evaluated as a function of the time referring to the test for evaluation of the reduction of the erythema by using the composition of the invention (called NT1123-12-A).

FIG. 14 refers to the average value of the reduction the erythema (% RE) for the product and control evaluated as a function of the time referring to the test for evaluation of the reduction of erythema by using the composition of the invention (called NT1123-12-A).

FIG. 15 refers to the average value of the intensity of the erythema (+a*) for the product and control evaluated referring to the test for evaluation of the reduction of erythema by using the composition of the invention (called NT1123-12-A).

FIG. 16 refers to percentage of reduction of the intensity of the erythema (% RIE) as a function of the time referring to the test for evaluation of the reduction of erythema by using the composition of the invention (called NT1123-13-A).

FIG. 17 refers to the result of treatment average as a function of the test for instrumental evaluation of the effect of the composition of the invention (called 12-33171-07) versus control composition on erythema induced by the tape-stripping technique.

FIG. 18 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition of the invention (called 12-33171-7) versus control composition on erythema induced by the tape-stripping technique.

FIG. 19 refers to the result of average difference as a function of the time T0 of the test for instrumental evaluation of the effect of the composition of the invention (called 12-33171-07) versus control composition on erythema induced by the tape-stripping technique.

DETAILED DESCRIPTION OF THE INVENTION

The antiperspirant deodorant cosmetic compositions with dermo-calming action of the present invention comprise 2-methyl-5-cyclohexylpentanol and aluminum hydrochloride and derivatives thereof as active ingredients, as well as cosmetically acceptably adjuvants.

Said adjuvants suitable for the purposes of the cosmetic compositions of the invention are selected, for example, from the group consisting of demineralized water, oils, emulsifiers, preservatives, sequestrants (chelating agents), fragrance and others cosmetically acceptable components.

A few examples of inert adjuvants and constituents compatible with the properties of the compositions described herein and that, additionally, may be employed in the present cosmetic composition are given hereinafter—in a non-restrictive, but only demonstrative manner

• • Water: water is the base of a number of preferred embodiments of the cosmetic composition of the present invention, acting as a carrier for other components. The compositions of the present invention comprise water, preferably demineralized or distilled at a suitable percentage (q.s.p.) for reaching 100% of the formula, based on the total weight of the present composition. Naturally, one may use other cosmetically acceptable carriers in the present invention;
  • skin conditioning agent pantenol;
  • emollients: olus oil, stearylic PPG-15 ether, dicapryl carbonate, silicones, cyclometicone, dimeticonol, cyclopentasyloxane, hydrogenated palm oil;
  • antioxidant agents: butylated hydroxidetoluene (BHT), butylated hydroxide anisol (BHA), among other;
  • chelating agents: EDTA, among others;
  • consistency agents: silica dimethyl sililate, magnesium silicate (talc), ceresin wax, hydroxypropyl starch phosphate; and
  • emulsifying agents: steareth-2, steareth-21, cetostearyl alcohol, ceteareth-20.

The composition according to the present invention may be present in different cosmetic forms as, for instance, and without any limitation, in the form of roll-on or cream deodorant.

According to a preferred embodiment of the present invention, the deodorant cosmetic composition of the present invention comprises:

• • 2-methyl-5-cyclohexylpentanol in an amount ranging from 0.1 to 1% by weight, preferably from 0.3 to 0.5%, more preferably 0.4% as a deodorant active ingredient;
  • 50% solution of aluminum hydrochloride in an amount ranging from 5.0 to 40% by weight, preferably from 10 to 35%, more preferably 30%, as an active ingredient and antiperspirant agent;
  • Pantenol in an amount ranging from 0.5 to 5% by weight, preferably from 0.8 to 3%, more preferably from 1 to 1.5% as a skin conditioning agent;
  • BHT in an amount ranging from 0.1 to 0.5% by weight, preferably from 0.04 to 0.3%, more preferably 0.05% as an antioxidant agent;
  • DMDM hydantoin in an amount ranging from 0.1 to 1% by weight, preferably from 0.3 to 0.8%, more preferably 0.6% as a preservative agent;
  • EDTA in an amount ranging from 0.05 to 0.5% by weight, preferably from 0.08 to 0.2%, more preferably 0.1% as a chelating agent;
  • Silica dimethyl silicate, magnesium silicate (talc), ceresin wax, hydroxypropylic starch phosphate in an amount ranging from 0.05 to 6% by weight, preferably from 0.08 to 5%, more preferably from 0.15 to 4%, as a consistency agent;
  • Olus soil, stearylic PPG-15 ether, hydrogenated palm oil, dicapryl carbonate, cyclomethicone silicones, dimethiconol, cyclopentasiloxane, in an amount ranging from 0.5 to 15% by weight, preferably from 0.8 to 10%, more preferably from 0.1 to 7% as emollients; and
  • Steareth-2, steareth-21, cetostearyl alcohol, ceteareth-20 in an amount ranging from 0.5 to 15% by weight, preferably from 1.0 to 10%, more preferably from 1.1 to 9.5% as emulsifying agents.

The antiperspirant deodorant cosmetic composition with dermo-calming action of the present invention has a number of advantages and desired characteristics with the ideal and balanced combination between its components, some of which are listed below:

• • differentiated antiperspirant protection;
  • differentiated viscosity;
  • differentiated hydration;
  • protective film characteristic;
  • differentiated softness; and
  • dermo-calming action, particularly for sensitized skins.

The embodiments of the invention exemplified hereinafter are intended to illustrate, without limiting, the scope of their object.

EXAMPLES

Example 1

The Cosmetic Composition of the Present Invention in Roll-on Form (Called 12-33171-07)

Table 1 below presents an example of formulation of the cosmetic composition according to the present invention in roll-on form.

TABLE 1
Component	Concentration (% by weight)

Demineralized water	56.3
Aluminum hydrochloride (50% solution)	30.0
Olus oil	3.8
Steareth-2	3.0
Hydroxypropylic starch phosphate	1.5
Steareth-21	1.1
Stearylic PPG-15 ether	1.0
Perfume	1.0
Pantenol	1.0
DMDM hydantoin	0.6
2-methyl-5-cyclohexylpentanol	0.4
Silica dimethyl silicate	0.15
Disodium EDTA	0.1
BHT	0.05

Example 2

The Cosmetic Composition of the Present Invention in Roll-on Form (Called 13-39540-01) without Olus Oil

Table 2 below presents one more example of formulation of the cosmetic composition according to the present invention in roll-on form.

TABLE 2
Component	Concentration (wt.-%)

Demineralized water	60.1
Aluminum hydrochloride (50% solution)	30.0
Steareth-2	3.0
Hydroxypropylic starch phosphate	1.5
Steareth-21	1.1
Stearylic PPG-15 ether	1.0
Perfume	1.0
Pantenol	1.0
DMDM hidantoin	0.6
2-methyl-5-cyclohexylpentanol	0.4
Silica dimethyl silicate	0.15
Disodium EDTA	0.1
BHT	0.05

Example 3

The Composition of the Present Invention in Roll-On Form (Called 13-39540-02 (with Palm Oil)

Table 3 below presents one more example of formulation of the cosmetic composition according to the present invention in roll-on form.

TABLE 3
Component	Concentration (wt.-%)

Demineralized water	59.1
Aluminum hydrochloride (50% solution)	30.0
Steareth-2	3.0
Hydroxypropylic starch phosphate	1.5
Steareth-21	1.1
Stearylic PPG-15 ether	1.0
Hydrogenated palm oil	1.0
Perfume	1.0
Pantenol	1.0
DMDM hydantoin	0.6
2-methyl-5-cyclohexylpentanol	0.4
Silica dimethyl silicate	0.15
Disodium EDTA	0.1
BHT	0.05

Example 4

The Cosmetic Composition of the Present Invention in Cream Form (Deo Cream NT1123-12-A)

Table 4 below presents a formulation of the cosmetic composition according to the present invention in cream form.

	TABLE 4
	Component	Concentration (wt.-%)

	Demineralized water	41.7
	Aluminum hydrochloride	30.0
	Cetosterayl alcohol	7.5
	Olus oil	3.8
	Ceresin	3.0
	Cyclopentasyloxane	2.5
	Talc	2.0
	Hydroxypropylic starch phosphate	2.0
	Steareth-20	1.75
	Pantenol	1.5
	Perfume	1.1
	Dicapryl carbonate	1.0
	Dimethiconol, cyclopentasiloxane	1.0
	DMDM hydantoin	0.6
	2-methyl-5-cyclohexylpentanol	0.4
	Disodium EDTA	0.1
	BHT	0.05

Example 5

The Cosmetic Composition of the Present Invention in Cream Form (Called 13-39540-03)

Table 5 below presents a formulation of the cosmetic composition according to the present invention in cream form.

	TABLE 5
	Component	Concentration (wt.-%)

	Demineralized water	45.5
	Aluminum hydrochloride	30.0
	Cetosterayl alcohol	7.5
	Ceresin	3.0
	Cyclopentasiloxane	2.5
	Talc	2.0
	Hydroxypropylic starch phostate	2.0
	Ceteareth-20	1.75
	Pantenol	1.5
	Perfume	1.1
	Dicapryl carbonate	1.0
	Dimethiconol, cyclopeontasiloxane	1.0
	DMDM hydantoin	0.6
	2.-methyl-5-cyclohexylpoentanol	0.4
	Disodium EDTA	0.1
	BHT	0.05

Example 6

The Cosmetic Composition of the Present Invention in Cream Form (Called 13-39540-04)

Table 6 below presents a formulation of the cosmetic composition according to the present invention in cream form.

	TABLE 6
	Component	Concentration (wt.-%)

	Demineralized water	44.5
	Aluminum hydrochloride	30.0
	Cetostearyl alcohol	7.5
	Cerasin	3.0
	cyclopeontasiloxane	2.5
	Talc	2.0
	Hydroxypropylic starch phosphate	2.0
	Ceteareth-20	1.75
	Pantenol	1.5
	Perfume	1.1
	Hydrogenated palm oil	1.0
	Dicapryl carbonate	1.0
	Dimethiconol, cyclopentasiloxane	1.0
	DMDM hydantoin	0.6
	2-methyl-5-cydohexylpentanol	0.4
	Disodium EDTA	0.1
	BHT	0.05

The cosmetic composition of the present invention is prepared in a conventional way, known to those skilled in the art.

Tests:

Test 1—Instrumental Evaluation of the Effect of the Composition of the Invention (Called 13-39540-03) on Erythema Caused by the Tape-Stripping Technique.

1.1—Objective

Evaluating the potential of a calming action of a topical product referring to a composition according to the invention through instrumental measurements of colorimetry.

1.2 Methodology, Materials and Equipment

Two symmetrical 10 cm² areas having randomized distribution in the front region of the forearms of the patients (a total of 21 participants) were demarcated. One of the areas was used for application of the product and the other was kept as control (untreated area). Colorimetric measurements were made with the equipment Mexameter MX18-Courge+Khazaka prior to tape-stripping removal (Fita Hipoalergênica Transproe^MR) and application of the product (Tb) after 30 tape-stripping removals at each site (T0) and after 30 minutes, 1, 2, 3, 4, 5 and 6 hours from application of the product.

1.3—Measurement of Erythema-Mexametry

The measurements were carried out by using the equipment Mexameter MX 18, Courage+Khazaka electronic GmbH through a measurement probe. The readings were made by applying the probe to the test areas with the pressure permitted by the spring (0.5 N).

The measurement area was 5 mm in diameter. Three measurements were carried out in each area. The measurement consisted in measuring the light absorbed and reflected at the wavelengths for green and red for hemoglobin and wavelengths for green and near infrared for melanin.

The operator positioned the probe vertically, forming a 90-degree angle with the skin and cleaned the probe with the aid of a very soft piece of paper prior to the first reading and between the readings of one area an another, even if it were the control area or the initial measurement of each area.

The reading indicated the degree of erythema of the skin. The scale of the equipment is arbitrary, the reading values indicating greater redness of the skin (erythema).

1.4—Steps of Research

1.4.1—First Step

• • The participants remained at rest in an air-conditioned room with temperature of 20±2° C. and relative humidity of 50±5% for at least 30 minutes prior to each reading;
  • The participants were told not to smoke; not to come out of the test room without prior authorization of the expert; not to come into contact with the area being tested at any place; not to contact the area being tested in contact with the clothes between the first air-conditioning and the end of the measurements; not to make abrupt movements with any part of the body; and not to allow the test area to get wet
  • The participants were evaluated by the dermatologist to confirm the research inclusion criteria;
  • Two symmetric 10 cm² areas of the region before the forearms having randomized distribution were demarcated. One area was used for application of the product and the other area was kept as negative control (untreated area); and
  • One determined the coloration of the areas through arithmetic mean of three measurements (Tb).

1.4.2—Second Step

• • 30 tape-stripping removals were carried out in the two demarcated areas. The adhesive tapes (TransporeMR) were replaced at each removal; and
  • One determined the coloration of the demarcated areas through the arithmetic mean of three measurements (T0).

1.4.3—Third Step

• • The tested product was applied in a randomized manner, in the amount of 0.02 g in the demarcated region of each participant. The product was spread over the skin with the aid of a latex fingerstall, with light and circular movements until the whole application area was entirely covered and homogeneous. The latex fingerstall was changed in each area;
  • The measurements were carried out in the following times:
  • T30min—thirty minutes after application of the product
  • T1h—one hour after application of the product
  • T2h—two hours after application of the product
  • T3h—three hours after application of the product;
  • T4h—four hours after application of the product;
  • T5h—five hours after application of the product;
  • T6h—six hours after application of the product.
  • The participants were evaluated by the dermatologist at the end of the measurements T6h; and
  • After the medical evaluation the participants were released.

1.5—Statistical Analysis

For a statistical analysis of the results, different tests were employed, as follows:

In order to compare the treatments in each time, one used ANOVA, followed by the DUNNET test and to compare the times with regard to the initial time T0, one used the Student test t.

As said before, the number of participants of the research was 21 and all of them completed the study in question.

The trust level considered in the comparative analyses was of 96%.

1.6—Results

1.6.1—Measurement of Erythema-Mexametry

TABLE 7
Measurements, descriptive statistics and results of the comparison

Participant of the

13-39540-03

Control

13-39540-03

Control

research	Tb	T0	Tb	T0	Δ(T0 − Tb)	Δ(T0 − Tb)

001	242	352	265	358	110	93
002	343	493	363	478	150	115
003	333	454	317	423	121	106
004	251	385	272	399	134	127
005	240	480	280	451	240	171
006	451	551	395	465	100	70
007	361	479	366	459	118	93
008	342	450	354	448	108	94
009	298	456	323	391	158	68
010	357	452	401	467	95	66
011	343	430	374	407	87	33
012	276	299	264	323	23	59
013	337	432	368	455	95	87
014	362	452	346	448	90	102
015	284	377	335	407	93	72
017	312	477	316	405	165	89
018	234	412	242	376	178	134
019	282	357	306	374	75	68
020	304	458	266	455	154	189
021	267	360	267	336	93	69
022	285	365	248	309	80	61
Average	309.7	427.2	317.5	411.1	117.5	93.6
Medium	304.0	450.0	317.0	407.0	108.0	89.0
Minimum	234.0	299.0	242.0	309.0	23.0	33.0
Maximum	451.0	551.0	401.0	478.0	240.0	189.0
Standard error	11.5	13.1	11.0	11.0	10.0	8.2
IC of 95%	[286.6;	[401.0;	[295.6;	[389.1;	[97.5;	[77.2;
	332.8]	453.3]	339.5]	433.2]	137.4]	110.0]

Δ (%) with respect to T0	37.9	29.5
% of participants with irritating effect	100.0	100.0
P-Value	<0.001***	<0.001***
***significant at level 0.1%;
**significant at level 1%;
*significant at level 5% (Student t test)

The T0 was higher on average than the Tb for product and control.

TABLE 8
Measurements and descriptive statistics of the product

									Δ(T30-
		T30-							min −
Participant	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h	T0)
001	352	217	216	270	265	300	292	275	−135
002	493	308	345	376	409	392	395	402	−185
003	454	225	266	328	337	368	343	346	−229
004	385	224	251	225	251	281	254	248	−161
005	480	326	353	348	361	365	379	378	−154
006	551	437	451	471	458	495	492	484	−114
007	479	370	358	353	369	379	389	381	−109
008	450	313	288	301	322	347	340	351	−137
009	456	332	350	339	389	387	384	380	−124
010	452	359	332	358	338	358	340	361	−93
011	430	320	311	328	309	308	339	351	−110
012	299	263	275	235	280	263	289	276	−36
013	432	373	358	353	380	382	376	360	−59
014	452	344	352	368	358	356	361	364	−108
015	377	278	273	279	300	309	311	323	−99
017	477	320	347	372	377	400	394	376	−157
018	412	240	240	266	257	265	278	264	−172
019	357	244	248	270	270	264	283	290	−113
020	458	393	366	401	398	407	442	401	−65
021	360	254	293	282	305	326	307	337	−106
022	365	305	277	287	292	252	274	280	−60
Average	427.2	306.9	311.9	324.3	334.5	343.0	345.8	344.2	−120.3
Medium	450.0	313.0	311.0	328.0	337.0	356.0	340.0	351.0	−113.0
Minimum	299.0	217.0	216.0	225.0	251.0	252.0	254.0	248.0	−229.0
Maximum	551.0	437.0	451.0	471.0	458.0	495.0	492.0	484.0	−36.0
Standard	13.1	13.3	12.3	13.0	12.3	13.3	13.1	12.4	10.1
error
IC de	[401.0;	[280.4;	[287.4;	[298.3;	[309.9;	[316.4;	[319.6;	[319.4;	[−140.5;
95%	453.3]	333.4]	336.5]	350.2]	359.2]	369.7]	372.0]	369.0]	−100.1]

Δ (%) with respect to the T0	−28.2

		Δ(T1 h −	Δ(T2 h −	Δ(T3 h −	Δ(T4 h −	Δ(T5 h −	Δ(T6 h −
	Participant	T0)	T0)	T0)	T0)	T0)	T0)
	001	−136	−82	−87	−52	−60	−77
	002	−148	−117	−84	−101	−98	−91
	003	−188	−126	−117	−86	−111	−108
	004	−134	−160	−134	−104	−131	−137
	005	−127	−132	−119	−115	−101	−102
	006	−100	−80	−93	−56	−59	−67
	007	−121	−126	−110	−100	−90	−98
	008	−162	−149	−128	−103	−110	−99
	009	−106	−117	−67	−69	−72	−76
	010	−120	−94	−114	−94	−112	−91
	011	−119	−102	−121	−122	−91	−79
	012	−24	−64	−19	−36	−10	−23
	013	−74	−79	−52	−50	−56	−72
	014	−100	−84	−94	−96	−91	−88
	015	−104	−98	−77	−68	−66	−54
	017	−130	−105	−100	−77	−83	−101
	018	−172	−146	−155	−147	−134	−148
	019	−109	−87	−87	−93	−74	−67
	020	−92	−57	−60	−51	−16	−57
	021	−67	−78	−55	−34	−53	−23
	022	−88	−78	−73	−113	−91	−85
	Average	−115.3	−102.9	−92.7	−84.1	−81.4	−83.0
	Medium	−119.0	−98.0	−93.0	−93.0	−90.0	−85.0
	Minimum	−188.0	−160.0	−155.0	−147.0	−134.0	−148.0
	Maximum	−24.0	−57.0	−19.0	−34.0	−10.0	−23.0
	Standard	8.1	6.3	7.0	6.6	7.1	6.6
	error
	IC de	[−131.4;	[−115.5;	[−106.7;	[−97.3;	[−95.5;	[−96.3;
	95%	−99.2]	−90.3]	−78.6]	−71.0]	−67.2]	−69.7]

	Δ (%) with	−27.0	−24.1	−21.7	−19.7	−19.1	−19.4
	respect to
	the T0

TABLE 9
Descriptive measurements and statistics of the control

									Δ(T30-
		T30-							min −
Participant	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h	T0)
001	358	261	281	290	320	332	335	346	−97
002	478	397	429	399	421	413	422	433	−81
003	423	289	328	319	321	346	331	332	−134
004	399	231	266	261	268	293	277	286	−168
005	451	349	344	349	392	346	366	361	−102
006	465	416	411	391	402	406	399	389	−49
007	459	387	372	351	356	375	384	367	−72
008	448	356	334	344	346	377	359	367	−92
009	391	356	361	343	354	365	361	364	−35
010	467	393	382	385	375	428	394	379	−74
011	407	347	334	331	352	353	364	360	−60
012	323	270	275	235	259	250	260	270	−53
013	455	437	425	405	429	422	403	416	−18
014	448	363	354	380	386	389	375	371	−85
015	407	328	336	323	324	344	331	349	−79
017	405	293	316	332	340	352	338	353	−112
018	376	217	219	240	269	277	282	257	−159
019	374	272	291	276	289	284	304	295	−102
020	455	365	346	326	324	349	347	350	−90
021	336	267	258	275	297	302	302	328	−69
022	309	278	260	247	240	226	203	223	−31
Average	411.1	327.2	329.6	323.9	336.4	344.2	339.9	342.7	−83.9
Medium	407.0	347.0	334.0	331.0	340.0	349.0	347.0	353.0	−81.0
Minimum	309.0	217.0	219.0	235.0	240.0	226.0	203.0	223.0	−168.0
Maximum	478.0	437.0	429.0	405.0	429.0	428.0	422.0	433.0	−18.0
Standard	11.0	13.7	12.5	11.6	11.7	12.1	11.7	11.2	8.4
error
IC of	[389.1;	[299.9;	[304.6;	[300.7;	[313.0;	[320;	[316.4;	[320.2;	[−100.7;
95%	433.2]	354.6]	354.6]	347.1]	359.7]	368.5]	363.3]	365.1]	−67.1]

Δ (%) em relação ao T0	−20.4

		Δ(T1 h −	Δ(T2 h −	Δ(T3 h −	Δ(T4 h −	Δ(T5 h −	Δ(T6 h −
	Participant	T0)	T0)	T0)	T0)	T0)	T0)
	001	−77	−68	−38	−26	−23	−12
	002	−49	−79	−57	−65	−56	−45
	003	−95	−104	−102	−77	−92	−91
	004	−133	−138	−131	−106	−122	−113
	005	−107	−102	−59	−105	−85	−90
	006	−54	−74	−63	−59	−66	−76
	007	−87	−108	−103	−84	−75	−92
	008	−114	−104	−102	−71	−89	−81
	009	−30	−48	−37	−26	−30	−27
	010	−85	−82	−92	−39	−73	−88
	011	−73	−76	−55	−54	−43	−47
	012	−48	−88	−64	−73	−63	−53
	013	−30	−50	−26	−33	−52	−39
	014	−94	−68	−62	−59	−73	−77
	015	−71	−84	−83	−63	−76	−58
	017	−89	−73	−65	−53	−67	−52
	018	−157	−136	−107	−99	−94	−119
	019	−83	−98	−85	−90	−70	−79
	020	−109	−129	−131	−106	−108	−105
	021	−78	−61	−39	−34	−34	−8
	022	−49	−62	−69	−83	−106	−86
	Average	−81.5	−87.2	−74.8	−66.9	−71.3	−68.5
	Medium	−83.0	−82.0	−65.0	−65.0	−73.0	−77.0
	Minimum	−157.0	−138.0	−131.0	−106.0	−122.0	−119.0
	Maximum	−30.0	−48.0	−26.0	−26.0	−23.0	−8.0
	Standard	7.0	5.7	6.6	5.7	5.7	6.8
	error
	IC of	[−95.6;	[−98.6;	[−87.9;	[−78.3;	[−82.7;	[−82.1;
	95%	−67.5]	−75.8]	−61.7]	−55.5]	−59.9]	−54.8]

	Δ (%) em	−19.8	−21.2	−18.2	−16.3	−17.3	−16.7
	relação
	ao T0

TABLE 10
Average and standard error of each treatment per time, and the difference
between the treatments

Product

Control

Product − Control

Time	Average	E.P.	Average	E.P.	Average	E.P.

T0		427.19	13.08	411.14	11.02	16.05	7.26
T30	min	306.90	13.26	327.24	13.69	−20.33	7.17
T1	h	311.90	12.28	329.62	12.49	−17.71	8.39
T2	h	324.29	12.98	323.90	11.60	0.38	7.82
T3	h	334.52	12.32	336.38	11.67	−1.86	8.05
T4	h	343.05	13.32	344.24	12.13	−1.19	8.48
T5	h	345.81	13.10	339.86	11.73	5.95	9.21
T6	h	344.19	12.40	342.67	11.24	1.52	8.23

TABLE 11
Porcentage of variation on the average with respect to the time T0,
and percentage of participants with positive and negative effect

Product - Control

	% of variation	% of participants	% of participants
	with respect	with positive	with negative

Time	to the T0	effect	effect

T30	min	−7.7	85.7	14.3
T1	h	−7.2	85.7	14.3
T2	h	−2.9	85.7	14.3
T3	h	−3.5	85.7	14.3
T4	h	−3.4	76.2	19.0
T5	h	−1.7	76.2	23.8
T6	h	−2.8	71.4	28.6

The product exhibited greater reduction with respect to the T0 in the average values of erythema compared with the control in the times T30min (p-value <0.0001), T1h (p-value=0.0001), T2h (p-value=0.0155), T3h (p-value=0.0253) and T4h (p-value=0.0163). No significant differences were found between the product and the control in the times T5h (p-value=0.2834) and T6h (p-value=0.0528).

The times T30min, T1h, T2h, T3h, T4h, T5h and T6h were lower than the time T0 for the product (p-values <0.001).

Wherein:

cm²: square centimeters;
g: grams;
h: hours;
no.: number;
° C.: degrees Centigrade;
Tx: time after x hours of application of the product.

1.7—Conclusion

After the statistical analysis of the results, one can conclude that the composition of the invention promoted reduction of the erythema caused by the tape-stripping technique until the time of 4 hours.

Test 2—Instrumental Evaluation of the Effect of the Composition of the Invention (Called 13-29540-04) on the Erythema Caused by the Tape-Stripping Technique

2.1—Objective

Evaluating the potential of calming action of a topical product referring to a composition according to the invention through instrumental colorimetric measurement.

2.2—Methodology, Materials and Equipment

Two symmetric 10 cm² areas of randomized distribution in the region before the forearms of the participants (a total of 21 participants) were demarcated. One of the areas was used for application of the product and the other was kept as control (untreated area). Colorimetric measurements were made with the equipment Mexameter MX18-Courage+Khazaka before tape-stripping removal (Fita Hipoalergên Transpore^MR) and application of the product (Tb), after the 30 tape-stripping removals at each site (T0) and after 30 minutes, 1, 2, 3, 4, 5 and 6 hours of application of the product.

2.3—Measurement of Erythema-Mexametry

The measurements were carried out by using the equipment Mexameter MX 18, Courage+Khazaka electronic GmbH through a measurement probe. The readings were made by applying the probe to the test areas with the pressure permitted by the spring (0.5 N).

The measurement area was 5 mm in diameter. Three measurements were carried out in each area. The measurement consisted in measuring the light absorbed and reflected at the wavelengths for green and red for hemoglobin and wavelengths for green and near infrared for melanin.

The operator positioned the probe vertically, forming a 90-degree angle with the skin and cleaned the probe with the aid of a very soft piece of paper prior to the first reading and between the readings of one area an another, even if it were the control area or the initial measurement of each area.

The reading indicated the degree of erythema of the skin. The scale of the equipment is arbitrary, the reading values indicating greater redness of the skin (erythema).

2.4—Steps of Research

2.4.1—First Step

• • The participants remained at rest in an air-conditioned room with temperature of 20±2° C. and relative humidity of 50±5% for at least 30 minutes prior to each reading;
  • The participants were told not to smoke; not to come out of the test room without prior authorization of the expert; not to come into contact with the area being tested at any place; not to contact the area being tested in contact with the clothes between the first air-conditioning and the end of the measurements; not to make abrupt movements with any part of the body; and not to allow the test area to get wet
  • The participants were evaluated by the dermatologist to confirm the research inclusion criteria;
  • Two symmetric 10 cm² areas of the region before the forearms having randomized distribution were demarcated. One area was used for application of the product and the other area was kept as negative control (untreated area); and
  • One determined the coloration of the areas through arithmetic mean of three measurements (Tb).

2.4.2—Second Step

• • 30 tape-stripping removals were carried out in the two demarcated areas. The adhesive tapes (TransporeMR) were replaced at each removal; and
  • One determined the coloration of the demarcated areas through the arithmetic mean of three measurements (T0).

2.4.3—Third Step

• • The tested product was applied in a randomized manner, in the amount of 0.02 g in the demarcated region of each participant. The product was spread over the skin with the aid of a latex fingerstall, with light and circular movements until the whole application area was entirely covered and homogeneous. The latex fingerstall was changed in each area;
  • The measurements were carried out in the following times:
  • T30min—thirty minutes after application of the product
  • T1h—one hour after application of the product
  • T2h—two hours after application of the product
  • T3h—three hours after application of the product;
  • T4h—four hours after application of the product;
  • T5h—five hours after application of the product;
  • T6h—six hours after application of the product.
  • The participants were evaluated by the dermatologist at the end of the measurements T6h; and
  • After the medical evaluation the participants were released.

2.5—Statistical Analysis

For a statistical analysis of the results, different tests were employed, as follows:

In order to compare the treatments in each time, one used ANOVA, followed by the DUNNET test and to compare the times with regard to the initial time T0, one used the Student test t.

As said before, the number of participants of the research was 21 and all of them completed the study in question.

The trust level considered in the comparative analyses was of 96%.

2.6—Results

2.6.1—Measurement of Erythema-Mexametry

TABLE 12
Measurements, descriptive statistics and results of the comparison

Participant

of the

13-39540-04

Control

13-39540-04

Control

research	Tb	T0	Tb	T0	Δ(T0 − Tb)	Δ(T0 − Tb)

001	279	374	265	358	95	93
002	300	426	363	478	126	115
003	303	428	317	423	125	106
004	264	395	272	399	131	127
005	236	412	280	451	176	171
006	403	505	395	465	102	70
007	403	484	366	459	81	93
008	358	442	354	448	84	94
009	309	428	323	391	119	68
010	383	459	401	467	76	66
011	350	417	374	407	67	33
012	313	389	264	323	76	59
013	360	407	368	455	47	87
014	326	388	346	448	62	102
015	302	398	335	407	96	72
017	304	344	316	405	40	89
018	244	423	242	376	179	134
019	279	383	306	374	104	68
020	306	410	266	455	104	189
021	220	371	267	336	151	69
022	270	301	248	309	31	61
Average	310.1	408.8	317.5	411.1	98.7	93.6
Medium	304.0	410.0	317.0	407.0	96.0	89.0
Minimum	220.0	301.0	242.0	309.0	31.0	33.0
Maximum	403.0	505.0	401.0	478.0	179.0	189.0
Standard	11.2	9.8	11.0	11.0	8.8	8.2
error
IC of 95%	[287.6; 332.6]	[389.2; 428.3]	[295.6; 339.5]	[389.1; 433.2]	[81.0; 116.3]	[77.2; 110.0]

Δ(%) with respect to the T0	31.8	29.5
% of participants with irritating effect	100.0	100.0
P-Value	<0.001***	<0.001***
***significant at level 0.1%;
**significant at level 1%;
*significant at level 5% (t-Student test).

The T0 was hither on the average than the Tb for product and control

TABLE 13
Measurements and descriptive statistics of the product

Partici-		T30-
pant	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h
001	374	235	257	280	295	334	331	346
002	426	284	263	323	341	328	347	331
003	428	234	266	276	314	340	328	317
004	395	246	276	267	270	295	293	290
005	412	263	273	307	298	304	285	289
006	505	380	390	408	423	441	424	428
007	484	391	388	380	385	389	398	394
008	442	312	304	275	313	319	321	332
009	428	321	336	331	353	401	344	371
010	459	369	375	388	392	416	417	386
011	417	355	323	335	350	350	386	353
012	389	324	305	295	294	311	290	306
013	407	362	373	342	390	371	354	378
014	388	292	315	330	319	317	297	306
015	398	300	311	309	314	332	311	313
017	344	257	282	280	307	321	303	311
018	423	260	264	283	284	300	290	290
019	383	254	259	258	275	280	294	275
020	410	345	317	312	359	348	335	349
021	371	226	244	264	270	260	271	284
022	301	251	244	245	251	222	213	227
Average	408.8	298.1	303.1	309.0	323.7	332.3	325.3	327.4
Medium	410.0	292.0	304.0	307.0	314.0	328.0	321.0	317.0
Minimum	301.0	226.0	244.0	245.0	251.0	222.0	213.0	227.0
Maximum	505.0	391.0	390.0	408.0	423.0	441.0	424.0	428.0
Standard	9.8	11.6	10.3	9.7	10.2	11.3	11.1	10.3
error
IC of 95%	[389.2; 428.3]	[275.0; 321.2]	[282.5; 323.6]	[289.6; 328.3]	[303.3; 344.1]	[309.8; 354.9]	[303.1; 347.6]	[306.9; 348.0]

Δ(%) em relação ao T0

		Δ(T30-	Δ	Δ	Δ	Δ	Δ	Δ
	Partici-	min −	(T1 h −	(T2 h −	(T3 h −	(T4 h −	(T5 h −	(T6 h −
	pant	T0)	T0)	T0)	T0)	T0)	T0)	T0)
	001	−139	−117	−94	−79	−40	−43	−28
	002	−142	−163	−103	−85	−98	−79	−95
	003	−194	−162	−152	−114	−88	−100	−111
	004	−149	−119	−128	−125	−100	−102	−105
	005	−149	−139	−105	−114	−108	−127	−123
	006	−125	−115	−97	−82	−64	−81	−77
	007	−93	−96	−104	−99	−95	−86	−90
	008	−130	−138	−167	−129	−123	−121	−110
	009	−107	−92	−97	−75	−27	−84	−57
	010	−90	−84	−71	−67	−43	−42	−73
	011	−62	−94	−82	−67	−67	−31	−64
	012	−65	−84	−94	−95	−78	−99	−83
	013	−45	−34	−65	−17	−36	−53	−29
	014	−96	−73	−58	−69	−71	−91	−82
	015	−98	−87	−89	−84	−66	−87	−85
	017	−87	−62	−64	−37	−23	−41	−33
	018	−163	−159	−140	−139	−123	−133	−133
	019	−129	−124	−125	−108	−103	−89	−108
	020	−65	−93	−98	−51	−62	−75	−61
	021	−145	−127	−107	−101	−111	−100	−87
	022	−50	−57	−56	−50	−79	−88	−74
	Average	−110.6	−105.7	−99.8	−85.1	−76.4	−83.4	−81.3
	Medium	−107.0	−96.0	−97.0	−84.0	−78.0	−87.0	−83.0
	Minimum	−194.0	−163.0	−167.0	−139.0	−123.0	−133.0	−133.0
	Maximum	−45.0	−34.0	−56.0	−17.0	−23.0	−31.0	−28.0
	Standard	8.8	7.7	6.5	6.8	6.7	6.2	6.4
	error
	IC of 95%	[−128.3; −93.0]	[−121.1; −90.2]	[−112.9; −86.8]	[−98.7; −71.4]	[−89.8; −63.1]	[−95.8; −71.1]	[−94.1; −68.6]
	Δ(%) em	−27.1	−25.9	−24.4	−20.8	−18.7	−20.4	−19.9
	relação
	ao T0

TABLE 14
Measurements and descriptive statistics of the control

Partici-		T30-
pant	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h
001	358	261	281	290	320	332	335	346
002	478	397	429	399	421	413	422	433
003	423	289	328	319	321	346	331	332
004	399	231	266	261	268	293	277	286
005	451	349	344	349	392	346	366	361
006	465	416	411	391	402	406	399	389
007	459	387	372	351	356	375	384	367
008	448	356	334	344	346	377	359	367
009	391	356	361	343	354	365	361	364
010	467	393	382	385	375	428	394	379
011	407	347	334	331	352	353	364	360
012	323	270	275	235	259	250	260	270
013	455	437	425	405	429	422	403	416
014	448	363	354	380	386	389	375	371
015	407	328	336	323	324	344	331	349
017	405	293	316	332	340	352	338	353
018	376	217	219	240	269	277	282	257
019	374	272	291	276	289	284	304	295
020	455	365	346	326	324	349	347	350
021	336	267	258	275	297	302	302	328
022	309	278	260	247	240	226	203	223
Average	411.1	327.2	329.6	323.9	336.4	344.2	339.9	342.7
Medium	407.0	347.0	334.0	331.0	340.0	349.0	347.0	353.0
Minimum	309.0	217.0	219.0	235.0	240.0	226.0	203.0	223.0
Maximum	478.0	437.0	429.0	405.0	429.0	428.0	422.0	433.0
Standard	11.0	13.7	12.5	11.6	11.7	12.1	11.7	11.2
error
IC of 95%	[389.1; 433.2]	[299.9; 354.6]	[304.6; 354.6]	[300.7; 347.1]	[313.0; 359.7]	[320; 368.5]	[316.4; 363.3]	[320.2; 365.1]

Δ(%) wtih respect to the T0

		Δ(T30-	Δ	Δ	Δ	Δ	Δ	Δ
	Partici-	min −	(T1 h −	(T2 h −	(T3 h −	(T4 h −	(T5 h −	(T6 h −
	pant	T0)	T0)	T0)	T0)	T0)	T0)	T0)
	001	−97	−77	−68	−38	−26	−23	−12
	002	−81	−49	−79	−57	−65	−56	−45
	003	−134	−95	−104	−102	−77	−92	−91
	004	−168	−133	−138	−131	−106	−122	−113
	005	−102	−107	−102	−59	−105	−85	−90
	006	−49	−54	−74	−63	−59	−66	−76
	007	−72	−87	−108	−103	−84	−75	−92
	008	−92	−114	−104	−102	−71	−89	−81
	009	−35	−30	−48	−37	−26	−30	−27
	010	−74	−85	−82	−92	−39	−73	−88
	011	−60	−73	−76	−55	−54	−43	−47
	012	−53	−48	−88	−64	−73	−63	−53
	013	−18	−30	−50	−26	−33	−52	−39
	014	−85	−94	−68	−62	−59	−73	−77
	015	−79	−71	−84	−83	−63	−76	−58
	017	−112	−89	−73	−65	−53	−67	−52
	018	−159	−157	−136	−107	−99	−94	−119
	019	−102	−83	−98	−85	−90	−70	−79
	020	−90	−109	−129	−131	−106	−108	−105
	021	−69	−78	−61	−39	−34	−34	−8
	022	−31	−49	−62	−69	−83	−106	−86
	Average	−83.9	−81.5	−87.2	−74.8	−66.9	−71.3	−68.5
	Medium	−81.0	−83.0	−82.0	−65.0	−65.0	−73.0	−77.0
	Minimum	−168.0	−157.0	−138.0	−131.0	−106.0	−122.0	−119.0
	Maximum	−18.0	−30.0	−48.0	−26.0	−26.0	−23.0	−8.0
	Standard	8.4	7.0	5.7	6.6	5.7	5.7	6.8
	error
	IC of 95%	[−100.7; −67.1]	[−95.6; −67.5]	[−98.6; −75.8]	[−87.9; −61.7]	[−78.3; −55.5]	[−82.7; −59.9]	[−82.1; −54.8]
	Δ(%) wtih	−20.4	−19.8	−21.2	−18.2	−16.3	−17.3	−16.7
	respect
	to the T0

TABLE 15
Average and standard error of each treatment per time and the difference
between the treatments

Product

Control

Product − Cotrol

Time	Average	E.P.	Average	E.P.	Average	E.P.

T0		408.76	9.77	411.14	11.02	−2.38	8.14
T30	min	298.14	11.55	327.24	13.69	−29.10	8.74
T1	h	303.10	10.28	329.62	12.49	−26.52	9.26
T2	h	308.95	9.67	323.90	11.60	−14.95	7.92
T3	h	323.67	10.21	336.38	11.67	−12.71	7.88
T4	h	332.33	11.26	344.24	12.13	−11.90	8.05
T5	h	325.33	11.14	339.86	11.73	−14.52	7.56
T6	h	327.43	10.29	342.67	11.24	−15.24	8.17

TABLE 16
Porcentage of variation on the average with respect to the time T0,
and percentage of participants with positive and negative effect

Product - Control

	% of variation	% of subjects	% of subjects
	with respect	with positive	with negative

Time	to the T0	effect	effect

T30	min	−6.7	85.7	14.3
T1	h	−6.0	76.2	23.8
T2	h	−3.2	66.7	33.3
T3	h	−2.6	66.7	33.3
T4	h	−2.4	81.0	19.0
T5	h	−3.1	71.4	28.6
T6	h	−3.2	66.7	33.3

The product exhibited greater reduction with respect to the T0 in the average values of erythema compared with the control in the times T30min (p-value=0.0004) and T1h (p-value=0.0031). No significant differences were found between product and control in the times T2h (p-value=0.0571), T3h (p-value=o.0571), T3h (p-value=0.2448), T4h (p-value=0.2311), T5h (p-value=0.1731) and T6h (p-value=0.0925).

The times T30min, T1h, T2h, T3h, T4h, T5h and T6h were lower that the T0 for the product (p-values <0.001);

wherein:
cm2: square centimeters;
g: grams;
h: hours;
no.: number;
° C.: degrees Centigrade;
Tx: Time after x hours of application of the product.

2.7—Conclusion

After a statistic analysis of the results, one can conclude that the composition of the invention promoted reduction of the erythema caused by the tape-stripping technique until the time of 1 hour.

Test 3—Instrumental Evaluation of the Effect of the Composition of the Invention (Called 13-39540-01) on the Erythema Caused by the Tape-Stripping Technique

3.1—Objective

Evaluating the potential of a calming action of a topical product referring to a composition according to the invention through instrumental measurements of colorimetry.

3.2—Methodology. Materials and Equipment

Two symmetrical 10 cm² areas having randomized distribution in the front region of the forearms of the patients (a total of 21 participants) were demarcated. One of the areas was used for application of the product and the other was kept as control (untreated area). Colorimetric measurements were made with the equipment Mexameter MX18-Couage+Khazaka prior to tape-stripping removal (Fita Hipoalergênica Transproe^MR) and application of the product (Tb) after 30 tape-stripping removals at each site (T0) and after 30 minutes, 1, 2, 3, 4, 5 and 6 hours from application of the product.

3.3—Measurement of Erythema-Mexametry

The measurements were carried out by using the equipment Mexameter MX 18, Courage+Khazaka electronic GmbH through a measurement probe. The readings were made by applying the probe to the test areas with the pressure permitted by the spring (0.5 N).

The measurement area was 5 mm in diameter. Three measurements were carried out in each area. The measurement consisted in measuring the light absorbed and reflected at the wavelengths for green and red for hemoglobin and wavelengths for green and near infrared for melanin.

The operator positioned the probe vertically, forming a 90-degree angle with the skin and cleaned the probe with the aid of a very soft piece of paper prior to the first reading and between the readings of one area an another, even if it were the control area or the initial measurement of each area.

The reading indicated the degree of erythema of the skin. The scale of the equipment is arbitrary, the reading values indicating greater redness of the skin (erythema).

3.4—Steps of Research

3.4.1—First Step

• • The participants remained at rest in an air-conditioned room with temperature of 20±2° C. and relative humidity of 50±5% for at least 30 minutes prior to each reading;
  • The participants were told not to smoke; not to come out of the test room without prior authorization of the expert; not to come into contact with the area being tested at any place; not to contact the area being tested in contact with the clothes between the first air-conditioning and the end of the measurements; not to make abrupt movements with any part of the body; and not to allow the test area to get wet
  • The participants were evaluated by the dermatologist to confirm the research inclusion criteria;
  • Two symmetric 10 cm² areas of the region before the forearms having randomized distribution were demarcated. One area was used for application of the product and the other area was kept as negative control (untreated area); and
  • One determined the coloration of the areas through arithmetic mean of three measurements (Tb).

3.4.2—Second Step

• • 30 tape-stripping removals were carried out in the two demarcated areas. The adhesive tapes (TransporeMR) were replaced at each removal; and
  • One determined the coloration of the demarcated areas through the arithmetic mean of three measurements (T0).

3.4.3—Third Step

• • The tested product was applied in a randomized manner, in the amount of 0.02 g in the demarcated region of each participant. The product was spread over the skin with the aid of a latex fingerstall, with light and circular movements until the whole application area was entirely covered and homogeneous. The latex fingerstall was changed in each area;
  • The measurements were carried out in the following times:
  • T30min—thirty minutes after application of the product
  • T1h—one hour after application of the product
  • T2h—two hours after application of the product
  • T3h—three hours after application of the product;
  • T4h—four hours after application of the product;
  • T5h—five hours after application of the product;
  • T6h—six hours after application of the product.
  • The participants were evaluated by the dermatologist at the end of the measurements T6h; and
  • After the medical evaluation the participants were released.

3.5—Statistical Analysis

For a statistical analysis of the results, different tests were employed, as follows:

In order to compare the treatments in each time, one used ANOVA, followed by the DUNNET test and to compare the times with regard to the initial time T0, one used the Student test t.

As said before, the number of participants of the research was 21 and all of them completed the study in question.

The trust level considered in the comparative analyses was of 96%.

3.6—Results

3.6.1—Measurement of Erythema-Mexametry

TABLE 17
Measurements, descriptive statistics and results of the comparison

Participant da

13-39540-01

Control

13-39540-01

Control

pesquisa	Tb	T0	Tb	T0	Δ (T0 − Tb)	Δ (T0 − Tb)

001	338	428	334	428	90	94
002	252	400	278	401	148	123
003	221	354	207	291	133	84
004	292	391	269	396	99	127
005	326	433	334	389	107	55
006	176	323	178	334	147	156
007	365	479	342	451	114	109
008	303	397	268	393	94	125
009	311	421	339	420	110	81
010	245	398	248	391	153	143
011	209	356	238	350	147	112
012	230	363	247	361	133	114
013	278	383	304	486	105	182
014	340	415	347	436	75	89
015	237	318	225	322	81	97
016	228	352	258	368	124	110
017	270	381	234	339	111	105
018	284	411	311	406	127	95
019	226	318	231	318	92	87
020	288	425	263	372	137	109
021	300	362	292	365	62	73
Average	272.3	386.1	273.7	381.8	113.8	108.1
Medium	278.0	391.0	268.0	389.0	111.0	109.0
Minimum	176.0	318.0	178.0	291.0	62.0	55.0
Maximum	365.0	479.0	347.0	486.0	153.0	182.0
Standard error	10.8	9.1	10.5	10.4	5.7	6.3
IC of 95%	[250.8; 293.8]	[367.9; 404.3]	[252.6; 294.8]	[360.9; 402.6]	[102.4; 125.1]	[95.5; 120.7]

Δ (%) with respect to the T0	41.8	39.5
% of participants with irritating effect	100.0	100.0
P-Value	<0.001***	<0.001***
***significant at level 0.1%;
**significant at level 1%;
*significant at level 5% (t-Student test).

The T0 was higher on the average than the Tb for product and control

TABLE 18
Measurements and descriptive statistics of the product

									Δ (T30-
		T30-							min −
Participant	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h	T0)
001	428	331	345	371	371	366	376	364	−97
002	400	270	300	320	320	308	304	317	−130
003	354	247	260	232	261	209	219	234	−107
004	391	273	288	313	328	312	321	322	−118
005	433	298	305	303	302	314	336	346	−135
006	323	154	159	167	164	168	172	210	−169
007	479	328	325	300	360	386	376	389	−151
008	397	263	279	292	277	297	309	291	−134
009	421	302	312	326	336	332	351	339	−119
010	398	282	283	304	305	302	298	303	−116
011	356	232	234	241	245	252	276	257	−124
012	363	244	234	227	254	268	242	255	−119
013	383	288	283	303	306	325	319	335	−95
014	415	353	337	363	379	360	384	392	−62
015	318	287	277	291	291	300	307	319	−31
016	352	213	202	217	224	254	244	293	−139
017	381	280	318	317	315	319	321	326	−101
018	411	284	270	280	287	324	328	356	−127
019	318	230	226	239	272	255	264	260	−88
020	425	310	300	302	297	291	345	345	−115
021	362	328	317	320	356	353	333	352	−34
Average	386.1	276.0	278.8	287.0	297.6	299.8	306.0	314.5	−110.0
Medium	391.0	282.0	283.0	302.0	302.0	308.0	319.0	322.0	−118.0
Minimum	318.0	154.0	159.0	167.0	164.0	168.0	172.0	210.0	−169.0
Maximum	479.0	353.0	345.0	371.0	379.0	386.0	384.0	392.0	−31.0
Standard	9.1	10.0	10.1	10.9	11.3	11.4	11.8	10.8	7.5
error
IC of	[367.9;	[256;	[258.5;	[265.3;	[275.1;	[277;	[282.4;	[293;	[−125.1;
95%	404.3]	296.1]	299]	308.8]	320.1]	322.5]	329.5]	336.1]	−95]

Δ (%) with respect to the T0	−28.5

	Δ	Δ	Δ	Δ	Δ	Δ
	(T1 h −	(T2 h −	(T3 h −	(T4 h −	(T5 h −	(T6 h −
Participant	T0)	T0)	T0)	T0)	T0)	T0)
001	−83	−57	−57	−62	−52	−64
002	−100	−80	−80	−92	−96	−83
003	−94	−122	−93	−145	−135	−120
004	−103	−78	−63	−79	−70	−69
005	−128	−130	−131	−119	−97	−87
006	−164	−156	−159	−155	−151	−113
007	−154	−179	−119	−93	−103	−90
008	−118	−105	−120	−100	−88	−106
009	−109	−95	−85	−89	−70	−82
010	−115	−94	−93	−96	−100	−95
011	−122	−115	−111	−104	−80	−99
012	−129	−136	−109	−95	−121	−108
013	−100	−80	−77	−58	−64	−48
014	−78	−52	−36	−55	−31	−23
015	−41	−27	−27	−18	−11	1
016	−150	−135	−128	−98	−108	−59
017	−63	−64	−66	−62	−60	−55
018	−141	−131	−124	−87	−83	−55
019	−92	−79	−46	−63	−54	−58
020	−125	−123	−128	−134	−80	−80
021	−45	−42	−6	−9	−29	−10
Average	−107.3	−99.0	−88.5	−86.3	−80.1	−71.6
Medium	−109.0	−95.0	−93.0	−92.0	−80.0	−80.0
Minimum	−164.0	−179.0	−159.0	−155.0	−151.0	−120.0
Maximum	−41.0	−27.0	−6.0	−9.0	−11.0	1.0
Standard	7.3	8.6	8.7	8.0	7.6	7.2
error
IC of	[−122;	[−116.2;	[−105.8;	[−102.2;	[−95.3;	[−85.9; −57.2]
95%	−92.8]	−81.9]	−71.1]	−70.4]	−65]
Δ (%) with respect to the	−27.8	−25.7	−22.9	−22.4	−20.8	−18.5
T0

TABLE 19
Measurements and descriptive statistics of the control

									Δ (T30-
		T30-							min −
Participant	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h	T0)
001	428	340	351	382	381	384	357	379	−88
002	401	326	329	337	338	323	333	331	−75
003	291	245	243	250	249	246	241	234	−46
004	396	283	315	339	360	352	343	369	−113
005	389	325	324	331	319	333	349	344	−64
006	334	180	229	203	214	248	251	260	−154
007	451	323	360	337	349	382	307	348	−128
008	393	288	296	308	292	294	287	321	−105
009	420	361	343	348	368	365	398	383	−59
010	391	281	306	325	326	325	323	343	−110
011	350	268	267	262	285	293	306	310	−82
012	361	270	292	261	312	282	287	301	−91
013	486	366	377	388	385	399	392	408	−120
014	436	396	397	412	421	416	432	419	−40
015	322	270	277	262	267	275	296	294	−52
016	368	244	222	241	248	264	262	301	−124
017	339	288	293	310	303	301	305	296	−51
018	406	319	313	318	312	344	316	338	−87
019	318	245	225	256	260	260	270	276	−73
020	372	293	290	279	331	316	348	357	−79
021	365	305	296	278	308	313	329	316	−60
Average	381.8	296.0	302.1	306.0	315.6	319.8	320.6	329.9	−85.8
Medium	389.0	288.0	296.0	310.0	312.0	316.0	316.0	331.0	−82.0
Minimum	291.0	180.0	222.0	203.0	214.0	246.0	241.0	234.0	−154.0
Maximum	486.0	396.0	397.0	412.0	421.0	416.0	432.0	419.0	−40.0
Standard	10.4	10.7	10.6	11.7	11.3	10.9	10.7	10.2	6.7
error
IC of	[360.9;	[274.6;	[281;	[282.6;	[293.1;	[298;	[299.2;	[309.4;	[−99.2;
95%	402.6]	317.4]	323.3]	329.5]	338.2]	341.6]	341.9]	350.4]	−72.3]

Δ (%) with respect to the T0	−22.5

	Δ	Δ	Δ	Δ	Δ	Δ
	(T1 h −	(T2 h −	(T3 h −	(T4 h −	(T5 h −	(T6 h −
Participant	T0)	T0)	T0)	T0)	T0)	T0)
001	−77	−46	−47	−44	−71	−49
002	−72	−64	−63	−78	−68	−70
003	−48	−41	−42	−45	−50	−57
004	−81	−57	−36	−44	−53	−27
005	−65	−58	−70	−56	−40	−45
006	−105	−131	−120	−86	−83	−74
007	−91	−114	−102	−69	−144	−103
008	−97	−85	−101	−99	−106	−72
009	−77	−72	−52	−55	−22	−37
010	−85	−66	−65	−66	−68	−48
011	−83	−88	−65	−57	−44	−40
012	−69	−100	−49	−79	−74	−60
013	−109	−98	−101	−87	−94	−78
014	−39	−24	−15	−20	−4	−17
015	−45	−60	−55	−47	−26	−28
016	−146	−127	−120	−104	−106	−67
017	−46	−29	−36	−38	−34	−43
018	−93	−88	−94	−62	−90	−68
019	−93	−62	−58	−58	−48	−42
020	−82	−93	−41	−56	−24	−15
021	−69	−87	−57	−52	−36	−49
Average	−79.6	−75.7	−66.1	−62.0	−61.2	−51.9
Medium	−81.0	−72.0	−58.0	−57.0	−53.0	−49.0
Minimum	−146.0	−131.0	−120.0	−104.0	−144.0	−103.0
Maximum	−39.0	−24.0	−15.0	−20.0	−4.0	−15.0
Standard	5.4	6.4	6.4	4.6	7.5	4.8
error
IC of	[−90.4;	[−88.6;	[−78.9; −53.4]	[−71.1; −52.9]	[−76.2;	[−61.4; −42.4]
95%	−68.8]	−62.9]			−46.2]
Δ (%) with	−20.9	−19.8	−17.3	−16.2	−16.0	−13.6
respect to the T0

TABLE 20
Average and standard error of each treatment per time,
and of the difference between the treatments

Product

Control

Product − Control

Time	Average	E.P.	Average	E.P.	Average	E.P.

T0	386.10	9.10	381.76	10.42	4.33	7.32
T30 min	276.05	10.01	296.00	10.71	−19.95	5.77
T1 h	278.76	10.14	302.14	10.58	−23.38	6.72
T2 h	287.05	10.88	306.05	11.70	−19.00	6.01
T3 h	297.62	11.25	315.62	11.28	−18.00	6.53
T4 h	299.76	11.38	319.76	10.90	−20.00	6.49
T5 h	305.95	11.79	320.57	10.67	−14.62	7.50
T6 h	314.52	10.76	329.90	10.24	−15.38	7.05

TABLE 21
Porcentage of variation in the average with respect to the time
T0, and percentage of participants with positive and negative effect

Produto-Controle

	% of	% of	% of
	variation with	participants with	participants with
Time	respect to the T0	positive effect	negative effect

T30	min	−6.0	85.7	14.3
T1	h	−6.9	81.0	19.0
T2	h	−5.8	85.7	14.3
T3	h	−5.6	81.0	19.0
T4	h	−6.1	81.0	19.0
T5	h	−4.7	66.7	33.3
T6	h	−5.0	71.4	28.6

The product exhibited greater reduction with respect to the T0 in the average values of erythema compared with the control in the times T30min (p-value=0.0010). T1h (p-value=0.0001), T2h (p-value=0.0008), T3h (p-value=0.0050), T4h (p-value=0.0020), T5h (p-value=0.0136) and T6h (p-value=0.0031).

The times T30min, T1h, T3h, T4h, T5h and T6h were lower than the time T0 for the product (p-values <0.001).

Wherein:

Cm²: square centimeters;
G: grams;
H: hours;
No.: number;

° C.: Degrees Celsius;

Tx: Time after x hours of application of the product.

6.4—Conclusion

After a statistic analysis of the results, one can conclude that the composition of the invention promoted reduction of the erythema caused by the tape-stripping technique until the time of 6 hours.

Test 4—Instrumental Evaluation of the Effect of the Composition of the Invention (Called 13-39540-02) on the Erythema Caused by the Tape-Stripping Technique

4.1—Objective

TABLE 22
Measurements. descriptive statistics and results of the comparison

Participant of

13-39540-02

Control

13-39540-02

Control

the research	Tb	T0	Tb	T0	Δ (T0 − Tb)	Δ (T0 − Tb)

001	318	425	334	428	107	94
002	278	391	278	401	113	123
003	211	290	207	291	79	84
004	308	436	269	396	128	127
005	348	455	334	389	107	55
006	168	326	178	334	158	156
007	326	473	342	451	147	109
008	304	379	268	393	75	125
009	317	407	339	420	90	81
010	253	383	248	391	130	143
011	279	364	238	350	85	112
012	265	379	247	361	114	114
013	318	435	304	486	117	182
014	325	418	347	436	93	89
015	233	319	225	322	86	97
016	236	349	258	368	113	110
017	232	314	234	339	82	105
018	336	447	311	406	111	95
019	227	303	231	318	76	87
020	291	395	263	372	104	109
021	318	399	292	365	81	73
Average	280.5	385.1	273.7	381.8	104.6	108.1
Medium	291.0	391.0	268.0	389.0	107.0	109.0
Minimum	168.0	290.0	178.0	291.0	75.0	55.0
Maximum	348.0	473.0	347.0	486.0	158.0	182.0
Standard error	10.5	11.5	10.5	10.4	5.1	6.3
IC of 95%	[259.5; 301.6]	[362.1; 408.1]	[252.6; 294.8]	[360.9; 402.6]	[94.4; 114.7]	[95.5; 120.7]

Δ (%) with respect to the T0	37.3	39.5
% of participants with irritaging effect	100.0	100.0
P-Value	<0.001***	<0.001***
***significant at level 0.1%;
**significant at level 1%;
*significant at level 5% (t-Student test).

The T0 was higher on the average than the Tb for product and control

TABLE 23
Measurements and descriptive statistics of the product

									Δ (T30-
		T30-							min −
Participant	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h	T0)
001	425	326	358	363	396	373	372	359	−99
002	391	246	262	292	290	292	286	294	−145
003	290	216	193	196	213	195	192	202	−74
004	436	313	345	386	384	378	360	396	−123
005	455	290	301	297	303	310	336	364	−165
006	326	162	180	180	172	228	217	215	−164
007	473	315	337	312	325	355	327	360	−158
008	379	280	288	294	292	299	298	307	−99
009	407	312	324	319	326	328	337	326	−95
010	383	274	296	304	319	324	322	301	−109
011	364	284	271	271	281	279	289	289	−80
012	379	228	228	260	248	269	266	273	−151
013	435	391	390	405	408	415	415	421	−44
014	418	370	354	372	400	383	380	399	−48
015	319	293	281	274	290	275	281	297	−26
016	349	201	189	219	229	247	248	282	−148
017	314	248	238	269	272	264	270	269	−66
018	447	333	317	338	325	339	336	389	−114
019	303	216	209	224	243	241	253	259	−87
020	395	313	290	299	338	304	317	336	−82
021	399	355	347	339	386	379	353	381	−44
Averate	385.1	284.1	285.6	295.9	306.7	308.4	307.4	320.0	−101.0
Medium	391.0	290.0	290.0	297.0	303.0	304.0	317.0	307.0	−99.0
Minimum	290.0	162.0	180.0	180.0	172.0	195.0	192.0	202.0	−165.0
Maximum	473.0	391.0	390.0	405.0	408.0	415.0	415.0	421.0	−26.0
Standard	11.5	12.8	13.4	13.1	14.2	12.7	12.1	13.2	9.3
error
IC of	[362.1;	[258.5;	[258.9;	[269.6;	[278.3;	[282.9;	[283.1;	[293.5;	[−119.7;
95%	408.1]	309.7]	312.3]	322.1]	335]	333.9]	331.6]	346.4]	−82.3]

Δ (%) with respect to the T0	−26.2

	Δ	Δ	Δ	Δ	Δ	Δ
	(T1 h −	(T2 h −	(T3 h −	(T4 h −	(T5 h −	(T6 h −
Participant	T0)	T0)	T0)	T0)	T0)	T0)
001	−67	−62	−29	−52	−53	−66
002	−129	−99	−101	−99	−105	−97
003	−97	−94	−77	−95	−98	−88
004	−91	−50	−52	−58	−76	−40
005	−154	−158	−152	−145	−119	−91
006	−146	−146	−154	−98	−109	−111
007	−136	−161	−148	−118	−146	−113
008	−91	−85	−87	−80	−81	−72
009	−83	−88	−81	−79	−70	−81
010	−87	−79	−64	−59	−61	−82
011	−93	−93	−83	−85	−75	−75
012	−151	−119	−131	−110	−113	−106
013	−45	−30	−27	−20	−20	−14
014	−64	−46	−18	−35	−38	−19
015	−38	−45	−29	−44	−38	−22
016	−160	−130	−120	−102	−101	−67
017	−76	−45	−42	−50	−44	−45
018	−130	−109	−122	−108	−111	−58
019	−94	−79	−60	−62	−50	−44
020	−105	−96	−57	−91	−78	−59
021	−52	−60	−13	−20	−46	−18
Averate	−99.5	−89.2	−78.4	−76.7	−77.7	−65.1
Medium	−93.0	−88.0	−77.0	−80.0	−76.0	−67.0
Minimum	−160.0	−161.0	−154.0	−145.0	−146.0	−113.0
Maximum	−38.0	−30.0	−13.0	−20.0	−20.0	−14.0
Standard	8.0	8.3	9.9	7.3	7.2	6.8
error
IC of	[−115.6;	[−105.8;	[−98.3; −58.6]	[−91.2; −62.2]	[−92.1;	[−78.7; −51.6]
95%	−83.4]	−72.7]			−63.3]
Δ (%) with	−25.8	−23.2	−20.4	−19.9	−20.2	−16.9
respect to the
T0

TABLE 24
Measurements and descriptive statistics of the control

									Δ (T30-
		T30-							min −
Participant	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h	T0)
001	428	340	351	382	381	384	357	379	−88
002	401	326	329	337	338	323	333	331	−75
003	291	245	243	250	249	246	241	234	−46
004	396	283	315	339	360	352	343	369	−113
005	389	325	324	331	319	333	349	344	−64
006	334	180	229	203	214	248	251	260	−154
007	451	323	360	337	349	382	307	348	−128
008	393	288	296	308	292	294	287	321	−105
009	420	361	343	348	368	365	398	383	−59
010	391	281	306	325	326	325	323	343	−110
011	350	268	267	262	285	293	306	310	−82
012	361	270	292	261	312	282	287	301	−91
013	486	366	377	388	385	399	392	408	−120
014	436	396	397	412	421	416	432	419	−40
015	322	270	277	262	267	275	296	294	−52
016	368	244	222	241	248	264	262	301	−124
017	339	288	293	310	303	301	305	296	−51
018	406	319	313	318	312	344	316	338	−87
019	318	245	225	256	260	260	270	276	−73
020	372	293	290	279	331	316	348	357	−79
021	365	305	296	278	308	313	329	316	−60
Average	381.8	296.0	302.1	306.0	315.6	319.8	320.6	329.9	−85.8
Medium	389.0	288.0	296.0	310.0	312.0	316.0	316.0	331.0	−82.0
Minimum	291.0	180.0	222.0	203.0	214.0	246.0	241.0	234.0	−154.0
Maximum	486.0	396.0	397.0	412.0	421.0	416.0	432.0	419.0	−40.0
Standard	10.4	10.7	10.6	11.7	11.3	10.9	10.7	10.2	6.7
error
IC of	[360.9;	[274.6;	[281;	[282.6;	[293.1;	[298;	[299.2;	[309.4;	[−99.2;
95%	402.6]	317.4]	323.3]	329.5]	338.2]	341.6]	341.9]	350.4]	−72.3]

Δ (%) with respect to the T0	−22.5

	Δ	Δ	Δ	Δ	Δ	Δ
	(T1 h −	(T2 h −	(T3 h −	(T4 h −	(T5 h −	(T6 h −
Participant	T0)	T0)	T0)	T0)	T0)	T0)
001	−77	−46	−47	−44	−71	−49
002	−72	−64	−63	−78	−68	−70
003	−48	−41	−42	−45	−50	−57
004	−81	−57	−36	−44	−53	−27
005	−65	−58	−70	−56	−40	−45
006	−105	−131	−120	−86	−83	−74
007	−91	−114	−102	−69	−144	−103
008	−97	−85	−101	−99	−106	−72
009	−77	−72	−52	−55	−22	−37
010	−85	−66	−65	−66	−68	−48
011	−83	−88	−65	−57	−44	−40
012	−69	−100	−49	−79	−74	−60
013	−109	−98	−101	−87	−94	−78
014	−39	−24	−15	−20	−4	−17
015	−45	−60	−55	−47	−26	−28
016	−146	−127	−120	−104	−106	−67
017	−46	−29	−36	−38	−34	−43
018	−93	−88	−94	−62	−90	−68
019	−93	−62	−58	−58	−48	−42
020	−82	−93	−41	−56	−24	−15
021	−69	−87	−57	−52	−36	−49
Average	−79.6	−75.7	−66.1	−62.0	−61.2	−51.9
Medium	−81.0	−72.0	−58.0	−57.0	−53.0	−49.0
Minimum	−146.0	−131.0	−120.0	−104.0	−144.0	−103.0
Maximum	−39.0	−24.0	−15.0	−20.0	−4.0	−15.0
Standard	5.4	6.4	6.4	4.6	7.5	4.8
error
IC of	[−90.4;	[−88.6;	[−78.9; −53.4]	[−71.1; −52.9]	[−76.2;	[−61.4; −42.4]
95%	−68.8]	−62.9]			−46.2]
Δ (%) with	−20.9	−19.8	−17.3	−16.2	−16.0	−13.6
respect to the
T0

TABLE 25
Average and standard error of each treatment per time,
and of the difference between the treatments

Producut

Control

Product − Control

Time	Average	E.P.	Average	E.P.	Average	E.P.

T0	385.10	11.50	381.76	10.42	3.33	5.94
T30 min	284.10	12.78	296.00	10.71	−11.90	7.02
T1 h	285.62	13.35	302.14	10.58	−16.52	6.78
T2 h	295.86	13.13	306.05	11.70	−10.19	6.72
T3 h	306.67	14.18	315.62	11.28	−8.95	7.01
T4 h	308.43	12.74	319.76	10.90	−11.33	5.56
T5 h	307.38	12.12	320.57	10.67	−13.19	5.95
T6 h	319.95	13.24	329.90	10.24	−9.95	6.84

TABLE 26
Porcentage of variation in the average with respect to the time T0,
and percentage of participants with positive and negative effect

Product - Control

	% of variation	% of participants	% of participants
	with respect	with positive	with negative

Time	to the T0	effect	effect

T30	min	−3.8	71.4	28.6
T1	h	−5.0	76.2	23.8
T2	h	−3.3	76.2	19.0
T3	h	−3.0	66.7	28.6
T4	h	−3.7	71.4	28.6
T5	h	−4.2	76.2	23.8
T6	h	−3.3	71.4	19.0

The product exhibited greater reduction with respect to the T0 in the average values of erythema compared with the control in the times T30min (p-value=0.0416), T1h (p-value=0.0040), and T5h (p-value=0.332). No significant differences were found between product and control in the times T2h (p-value=0.0579), T3h (p-value=0.1489). T4h (p-value 0.0712), and T6h (p-value=0.0508).

The times T30, T1h, T2h, T3h, T4h, T5h and T6h were lower than the time T0 for the product (p-values<0.001).

Wherein:

Cm²: square centigrade:
G: grams;
H: hours;
No.: number;
° C.=degrees Celsius;
Tx: Time after x hours of application of the product.

6.5—Conclusion

• • After a statistical analysis of the results, one can conclude that the composition of the invention promoted reduction of the erythema caused by the tape-stripping technique until the time of 1 hour and in the time of 5 hours.

Test 5—Evaluation of the Reduction of Erythema Caused by the Tape-Stripping Technique by Using the Composition of the Invention (called NT1123-12-A).

5.1 Objective

Evaluating the efficacy of the topical product (called BDP 1160.18704.6) referring to a composition according to the in reducing skin erythema induced by mechanical insult and evaluated as a function of the redness of the skin. Ion this study, one evaluated the efficacy of a composition according to the invention (NT1123-12-A) in reducing cutaneous erythema with respect to a control (site without application of any products). The evaluations were carried in the following times:

t0: right after formation of the erythema induced by the tape-stripping method;

t0.5: 30 minutes after induction of the erythema and application or non-application of the product;

t1: 1 hour after induction of the erythema and application or non-application of the product;

t2: 2 hours after induction of the erythema and application or non-application of the product;

t3: 3 hours after induction of the erythema and application or non-application of the product;

t4: 4 hours after induction of the erythema and application or non-application of the product;

t5: 5 hours after induction of the erythema and application or non-application of the product.

5.2—Methodology, Materials and Equipment

On each voluntary woman (a total of 25 participants), two 2.5×4.0 cm rectangles were marked with a surgical pen, called sites, on the left or right forearm. After 30 minutes of air-conditioning, the environment controlled at 20±° C. and 50±5% of relative humidity of the air, 30 tape-stripping removals with Transpore® 3M tape were carried out at each site, followed by the measurements of erythema by the mexametry and colorimetry technique. These measurements were called basal measurements (t0). After the mechanical insult, the product was applied, and the voluntary women remained at the laboratory for the measurements after 0.5 (30 minutes), 1, 2, 3, 4, 5 and 6 hours. During the whole experiment the climatic conditions were kept constant according to the ranges cited before. At the site intended for the product, 80 μL of the sample under study was applied, one of the sites being used as control (without application of any products).

5.3—Acquisition of Measurements

The measurements were made by using a Mexameter® MX 18 probe, coupled to the equipment Multi Probe Adapter MPA-5 (CKeletronics, Germany). Concomitantly with the measurements, one used an automatized spreadsheet of the software Microsoft® Office Excel 2010 for calculation of the Variation Coefficient (VC/CV) of the readings obtained. One carried out 5 measurements per site in each time. If in 5 measurements the VC/CV presented a value lower than 4%, one would finish the measurements at the site and continue them in the next one; otherwise, the process was restarted by using the colorimeter Byk-Gardner Spectro-Guide Sphere Gloss. For this evaluation, one recorded only the values of a*, which is the axis that ranges from green (−120) to read (+120). The values were recorded on an automatized spreadsheet of the software Microsoft® Office Excel 2010 for calculation of the Coefficient of Variation (CV/VC) of the readings obtained. One carried out 3 measurements per site in each time. If in 3 measurements the CV/VC presented a value lower than 4%, one would finish the measurements at the site and continue the measurements at the next one; otherwise the process was restarted until a CV/VC lower than 4% would be obtained.

5.4—Results

5.4.1—Evaluation of the Reduction of the Erythema by Mexametry

In evaluating of the reduction of the erythema by mexametry, one measured the erythema values (E) for each voluntary woman, at the site intended for the product and at the control site. FIG. 13 shows the average values of Erythema (E) obtained for the product site and control site.

In order to evaluate the homogeneity of t erythema caused by the mechanical insult, the values of erythema measured at each site in the basal time (t0) were statistically compared with each other by using the t-Student test, in pairs, with trust interval of 95%. The result is summarized in Table 27.

TABLE 27
Comparison of the values of erythema induced
after mechanical insult - Value of P.

	Et0 product vs. Et0 control	0.5533 (non-significant)

According to the results obtained, there was no statistically significant difference between the sites (P>0.05), indicating the homogeneity in the values of erythema after the mechanical insult. This indicated that the study was conducted with homogeneous basal values of erythema at the evaluation sites.

In order to evaluate whether there were significant variations in the erythema along the study, the erythema measurements obtained after 0.5; 1; 2; 3; 4; 5 and 6 hours from application of the product, or the basal measurements (t0) were not compared, carried out right after the mechanical insult (prior to application of the product), by using the single-factor variance analysis method, with Dunnett post-test multiple comparison, considering α=0.05. The results of the statistical analysis are summarized in Table 28.

TABLE 28
Summarized data of the statistical analysis. Comparison of the values
of erythema formed after the mechanical insult (t0) vs ti (wherein
i = 0.5, 1, 2, 3, 4, 5 and 6 hours from application). P values

Comparison group	Control	NT1123-12-A
Et0 vs. Et0.5	P < 0.05 (significant)	P < 0.05 (significant)
Et0 vs. Et1	P < 0.05 (significant)	P < 0.05 (significant)
Et0 vs. Et2	P < 0.05 (significant)	P < 0.05 (significant)
Et0 vs. Et3	P < 0.05 (significant)	P < 0.05 (significant)
Et0 vs. Et4	P < 0.05 (significant)	P < 0.05 (significant)
Et0 vs. Et5	P < 0.05 (significant)	P < 0.05 (significant)
Et0 vs. Et6	P < 0.05 (significant)	P < 0.05 (significant)

According to the results, it was possible to find out that there was a statistically significant reduction (P<0.05) of the skin erythema after 0.5, 1, 2, 3, 4, 5 and h hours from application of the composition according to the invention as compared with the initial erythema (t0) and still that at the control site (without application of any products) was also obtained one observed a significant reduction (P<0.05) in the erythema formed by the mechanical insult after 0.5, 1, 2, 3, 4, 5 and 6 hours.

Although one has observed a reduction of the erythema at both sites along the study, it is possible to observe, in FIG. 14, which shows the percentage of Reduction of the Erythema (% RE) obtained in each evaluation time, what there was a more marked reduction of the erythema at the site intended for the product.

In order to evaluate the significance of the reduction of the erythema along the time, that is, the Calming Effect (EC/CE) provided by the product with respect to the control, one calculated the ratio between the erythema measurements after 0.5, 1, 2, 3, 4, 5 and 6 hours with respect to the value obtained right after the mechanical insult (t0), by using Equation 1.

EC=E_ti/E_t0

Equation 1. Calculation of the Calming Effect (EC). E_ti=measurement of the coloration of the erythema in the time i (i=0.5, 1, 2, 3, 4, 5 and 6h) and E_t0=measurement of the coloration of the basal erythema (right after formation).

The values of the Calming Effect obtained for the site with application of the product, in each time, were statistically compared with the values obtained for the control by using the t-Student test, bimodal, in pairs, with trust interval of 95%. The results of the statistical analysis are listed in Attachment VII and are summarized in Table 29.

TABLE 29
Comparison of the results in terms of EC between the product and the respective control.
P. values

Comparison
group	t0.5	t1	t2	t3	t4	t5	t6
ECNT1123-12-A	0.0014	0.0281	0.0563	0.0787	0.0528	0.1682	0.6979
vs. ECControl	(significant)	(significant)	(Non-	(Non-	(Non-	(Non-	(Non-
			significant)	significant)	significant)	significant)	significant)

The reduction of the skin erythema provided by the composition of the invention presented a statistically significant difference (P<0.05) after 30 minutes and 1 hour from application as compared with the respective control (site without application of any products). This indicated that the product was effective in reducing skin erythema by mechanical insult and evaluated as a function of the redness of the skin until 1 hour after application.

5.4.2—Evaluation of the Reduction of the Erythema by Colorimetry

In evaluating the reduction of the erythema by colorimetry, one measured the values of the coordinate *a for each volunteer at the site intended for the product and at the control site. FIG. 15 shows the average value of the Erythema Intensity (+a*).

In order to evaluate the homogeneity of the erythema formed by the mechanical insult, the values of a* measured at each site in the basal time (t0) were statistically compared by using the t-Student test, in pairs, with trust interval of 95%. The results achieved are summarized in table 30.

TABLE 30
Comparison of the values of the erythema occurrences
induced after mechanical insult. Value of P

	a*t0 product vs. a* t0 control	0.6682 (non-significant)

According to the results obtained, there was no statistically significant difference between the sites (P>0.05), indicating that there was homogeneity in the values of a* after the mechanical insult. This indicated that the study was conducted with homogeneous basal erythema values for the sites under evaluation.

In order to evaluate whether there were significant alterations in the erythema along the study, the erythema measurements obtained after 0.5, 1, 2, 3, 4, 5, and 6 hours from application of the product or non-application were compared with the basal measurements (t0) carried out right after the mechanical insult (prior to application of the product), by using the single-factor variance analysis, with post-test of Dunnett multiple comparison, considering α=0.0.05. The results of the statistical analysis are summarized in Table 31.

TABLE 31
Summarized data of the statistical analysis. Comparison of the values
of a* obtained after the mechanical insult (t0) vs. ti (wherein i =
0.5, 1, 2, 3, 4, 5 e 6 h from application), Values of P.

Comparison group	Control	NT1123-12-A
a*t0 vs. a*t0.5	P < 0.05 (significant)	P < 0.05 (significant)
a*t0 vs. a*t1	P < 0.05 (significant)	P < 0.05 (significant)
a*t0 vs. a*t2	P < 0.05 (significant)	P < 0.05 (significant)
a*t0 vs. a*t3	P < 0.05 (significant)	P < 0.05 (significant)
a*t0 vs. a*t4	P < 0.05 (significant)	P < 0.05 (significant)
a*t0 vs. a*t5	P < 0.05 (significant)	P < 0.05 (significant)
a*t0 vs. a*t6	P < 0.05 (significant)	P < 0.05 (significant)

According to the results, it was possible to observe that that was a statistically significant reduction (P<0.05) of the skin erythema after 0.5, 1, 2, 3, 4, 5, and 6 hours from application of the composition according to the invention as compared with the initial erythema (t0), and that in the control site (without application of any products) there was a significant reduction (P<0.05) in the erythema formed by the mechanical insult after 0.5, 1, 2, 3, 45, and 6 hours. Although there has been a reduction of the erythema at both sites along the study, it is possible to observe, in FIG. 16, which shows the percentage of Reduction of Erythema Intensity (% RIE) obtained in each evaluation time, that there was a greater reduction of the erythema at the site intended for the product.

In order to evaluate the Calming Effect (CE/EC), one calculated the ratio between the measurements of a* after 0.5, 1, 2, 3, 4, 5, and 6 hours with respect to the value obtained along the mechanical insult (t0), by using Equation 2.

EC=a*_ti/a*_t0

Equation 2—Calculation of the Calming Effect (EC). a*_ti=measurement of the coloration of the erythema in the time i (i=0.5, 1, 2, 3, 4, 5 e 6h) e a*_t0=measurement of the coloration of the basal erythema (right after formation)

The values of the Calming Effect achieved for the site with application of the product, in each time, were statistically compared with the values achieved for the control by using the t-Student test, bimodal, in pairs, with trust interval of 95%. The results of the statistical analysis are summarized in table 32.

TABLE 32
A comparison of the results in terms of EC between the product and the
respective control. Values of P.

Comparison
group	t0.5	t1	t2	t3	t4	t5	t6
ECNT1123-12-A	0.0358	0.0280	0.5951	0.4005	0.5370	0.7799	0.6547
vs. ECControle	(significant)	(significant)	(non-	(non-	(non-	(non-	(non-
			sitnificant)	significant)	significant)	significant)	significant)

The reduction of the skin erythema provided by the composition according to the invention shows a statistically significant difference (P<0.05) after 30 minutes and 1 hour from application as compared with the respective control (site without application of any products). This indicated that the product was effective in reducing the skin erythema induced by mechanical insult and evaluated as a function of the skin redness until 1 hour from application.

Test 6—Instrumental Test of the Effect of the Composition of the Invention (Called 12-33171-07) on the Erythema Caused by the Tape-Stripping Technique

6.1—Objective

Evaluating the potential of calming action of a topical product referring to a composition according to the invention through instrumental measurements of colorimetry.

6.2—Methodology. Materials and Equipment

Two symmetrical 10 cm² areas having randomized distribution in the front region of the forearms of the patients (a total of 19 participants) were demarcated. One of the areas was used for application of the product and the other was kept as control (untreated area). Colorimetric measurements were made with the equipment Mexameter MX18-Courage+Khazaka prior to tape-stripping removal (Fita Hipoalergênica Transproe^MR) and application of the product (Tb) after 30 tape-stripping removals at each site (T0) and after 30 minutes, 1, 2, 3, 4, 5 and 6 hours from application of the product.

6.3—Measurement of Erythema-Mexametry

The measurements were carried out by using the equipment Mexameter MX 18, Courage+Khazaka electronic GmbH through a measurement probe. The readings were made by applying the probe to the test areas with the pressure permitted by the spring (0.5 N).

The measurement area was 5 mm in diameter. Three measurements were carried out in each area. The measurement consisted in measuring the light absorbed and reflected at the wavelengths for green and red for hemoglobin and wavelengths for green and near infrared for melanin.

The operator positioned the probe vertically, forming a 90-degree angle with the skin and cleaned the probe with the aid of a very soft piece of paper prior to the first reading and between the readings of one area an another, even if it were the control area or the initial measurement of each area.

The reading indicated the degree of erythema of the skin. The scale of the equipment is arbitrary, the reading values indicating greater redness of the skin (erythema).

6.4—Steps of Research

6.4.1—First Step

• • The participants remained at rest in an air-conditioned room with temperature of 20±2° C. and relative humidity of 50±5% for at least 30 minutes prior to each reading;
  • The participants were told not to smoke; not to come out of the test room without prior authorization of the expert; not to come into contact with the area being tested at any place; not to contact the area being tested in contact with the clothes between the first air-conditioning and the end of the measurements; not to make abrupt movements with any part of the body; and not to allow the test area to get wet
  • The participants were evaluated by the dermatologist to confirm the research inclusion criteria;
  • Two symmetric 10 cm² areas of the region before the forearms having randomized distribution were demarcated. One area was used for application of the product and the other area was kept as negative control (untreated area); and
  • One determined the coloration of the areas through arithmetic mean of three measurements (Tb).

6.4.2—Second Step

• • 30 tape-stripping removals were carried out in the two demarcated areas. The adhesive tapes (TransporeMR) were replaced at each removal; and
  • One determined the coloration of the demarcated areas through the arithmetic mean of three measurements (T0).

6.4.3—Third Step

• • The tested product was applied in a randomized manner, in the amount of 0.02 g in the demarcated region of each participant. The product was spread over the skin with the aid of a latex fingerstall, with light and circular movements until the whole application area was entirely covered and homogeneous. The latex fingerstall was changed in each area;
  • The measurements were carried out in the following times:
  • T30min—thirty minutes after application of the product
  • T1h—one hour after application of the product
  • T2h—two hours after application of the product
  • T3h—three hours after application of the product;
  • T4h—four hours after application of the product;
  • T5h—five hours after application of the product;
  • T6h—six hours after application of the product.
  • The participants were evaluated by the dermatologist at the end of the measurements T6h; and
  • After the medical evaluation the participants were released.

6.5—Statistical Analysis

The software used in the analyses was MINITAB 14 AND XLSTAT 2012.

As said before, the number of participants in the research was 19

The trust level considered in the comparative analysis was of 95%.

6.6—Results

6.6.1—Erythema Measurement-Mexametry

TABLE 33
Measurements descriptive statistics and results of the comparison

12-33171-07

Control

12-33171-07

Control

Subject	Tb	T0	Tb	T0	Δ (T0 − Tb)	Δ (T0 − Tb)

002	222	325	224	291	103	67
004	262	293	264	322	31	58
005	173	291	198	256	118	58
006	255	346	267	323	91	56
007	147	346	174	213	199	39
008	238	369	246	338	131	92
009	209	258	209	334	49	125
010	157	266	192	172	109	−20
012	187	269	162	285	82	123
013	328	383	340	364	55	24
014	163	264	117	258	101	141
015	137	304	163	236	167	73
016	155	293	135	351	138	216
017	205	363	193	397	158	204
018	279	413	271	368	134	97
019	244	380	227	374	136	147
020	208	308	243	319	100	76
021	212	287	229	313	75	84
022	293	374	330	382	81	52
Average	214.4	322.7	220.2	310.3	108.3	90.1
Medium	209.0	308.0	224.0	322.0	103.0	76.0
Minimum	137.0	258.0	117.0	172.0	31.0	−20.0
Maximum	328.0	413.0	340.0	397.0	199.0	216.0
Standard erros	12.2	10.9	13.6	14.0	9.7	13.4
IC of 95%	[189.9;	[300.9;	[193; 247.4]	[282.3;	[88.9; 127.8]	[63.2; 117]
	238.9]	344.6]		338.3]

Δ (%) with respect to the T0	50.5	40.9
% of volunteers with irritating effect	100.0	94.7
P-Value	<0.001***	<0.001***
***significant at level 0.1%;
**significant at level 1%;
*significant at level 5% (t-Student test).

The time T0 was higher on the average than the time Tb for product and control

TABLE 34
Measurements and descriptive statistics of the product

									Δ (T30-
		T30-							min −
Subject	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h	T0)
002	325	214	210	204	224	248	248	227	−111
004	293	323	320	284	309	296	280	311	30
005	291	198	191	194	191	207	203	213	−93
006	346	289	232	259	243	262	240	245	−57
007	346	209	202	220	269	208	251	277	−137
008	369	278	269	267	266	250	264	242	−91
009	258	235	192	187	190	186	228	182	−23
010	266	193	190	229	225	227	231	233	−73
012	269	245	212	211	209	226	302	265	−24
013	383	276	319	325	320	305	336	350	−107
014	264	149	157	176	178	185	195	195	−115
015	304	200	214	191	194	204	214	244	−104
016	293	229	192	188	183	207	249	265	−64
017	363	225	191	255	206	248	260	249	−138
018	413	345	311	359	325	336	366	347	−68
019	380	335	312	267	255	316	287	308	−45
020	308	230	241	226	166	247	254	231	−78
021	287	191	194	196	176	197	190	225	−96
022	374	340	335	310	328	316	288	290	−34
Average	322.7	247.6	236.0	239.4	234.6	245.8	257.2	257.8	−75.2
Medium	308.0	230.0	212.0	226.0	224.0	247.0	251.0	245.0	−78.0
Minimum	258.0	149.0	157.0	176.0	166.0	185.0	190.0	182.0	−138.0
Maximum	413.0	345.0	335.0	359.0	328.0	336.0	366.0	350.0	30.0
Standard	10.9	13.2	12.9	12.0	12.5	10.9	10.5	10.7	9.8
error
IC of 95%	[300.9;	[221.2;	[210.1;	[215.4;	[209.5;	[224;	[236.2;	[236.5;	[−94.8;
	344.6]	273.9]	261.9]	263.4]	259.6]	267.7]	278.2]	279.2]	−55.5]

Δ (%) with respect to T0	−23.3

	Δ	Δ	Δ	Δ	Δ	Δ
	(T1 h −	(T2 h −	(T3 h −	(T4 h −	(T5 h −	(T6 h −
Subject	T0)	T0)	T0)	T0)	T0)	T0)
002	−115	−121	−101	−77	−77	−98
004	27	−9	16	3	−13	18
005	−100	−97	−100	−84	−88	−78
006	−114	−87	−103	−84	−106	−101
007	−144	−126	−77	−138	−95	−69
008	−100	−102	−103	−119	−105	−127
009	−66	−71	−68	−72	−30	−76
010	−76	−37	−41	−39	−35	−33
012	−57	−58	−60	−43	33	−4
013	−64	−58	−63	−78	−47	−33
014	−107	−88	−86	−79	−69	−69
015	−90	−113	−110	−100	−90	−60
016	−101	−105	−110	−86	−44	−28
017	−172	−108	−157	−115	−103	−114
018	−102	−54	−88	−77	−47	−66
019	−68	−113	−125	−64	−93	−72
020	−67	−82	−142	−61	−54	−77
021	−93	−91	−111	−90	−97	−62
022	−39	−64	−46	−58	−86	−84
Average	−86.7	−83.4	−88.2	−76.9	−65.6	−64.9
Medium	−93.0	−88.0	−100.0	−78.0	−77.0	−69.0
Minimum	−172.0	−126.0	−157.0	−138.0	−106.0	−127.0
Maximum	27.0	−9.0	16.0	3.0	33.0	18.0
Standard	9.6	7.1	9.1	7.2	8.5	8.3
error
IC of 95%	[−105.9;	[−97.5;	[−106.3;	[−91.3; −62.5]	[−82.6;	[−81.5; −48.3]
	−67.6]	−69.2]	−70.1]		−48.5]
Δ (%) with respect	−26.9	−25.8	−27.3	−23.8	−20.3	−20.1
to T0

TABLE 35
Measurements and descriptive statistics of the control

									Δ (T30-
		T30-							min −
Subject	T0	min	T1 h	T2 h	T3 h	T4 h	T5 h	T6 h	T0)
002	291	194	214	201	216	245	245	241	−97
004	322	327	326	283	301	318	314	297	5
005	256	193	178	189	189	189	210	196	−63
006	323	282	242	250	258	248	250	242	−41
007	213	175	181	176	217	198	226	221	−38
008	338	304	297	287	288	267	270	280	−34
009	334	259	231	213	202	176	228	200	−75
010	172	202	166	206	180	200	163	184	30
012	285	234	204	232	209	230	271	262	−51
013	364	279	299	329	365	329	349	352	−85
014	258	195	205	195	216	185	191	219	−63
015	236	160	151	147	156	212	189	194	−76
016	351	273	292	344	278	257	276	290	−78
017	397	238	218	251	209	257	251	260	−159
018	368	327	267	305	289	272	322	327	−41
019	374	298	290	264	235	329	320	311	−76
020	319	244	274	237	215	259	254	258	−75
021	313	235	235	228	233	248	246	238	−78
022	382	333	322	336	328	312	291	297	−49
Average	310.3	250.1	241.7	245.9	241.3	249.0	256.1	256.3	−60.2
Medium	322.0	244.0	235.0	237.0	217.0	248.0	251.0	258.0	−63.0
Minimum	172.0	160.0	151.0	147.0	156.0	176.0	163.0	184.0	−159.0
Maximum	397.0	333.0	326.0	344.0	365.0	329.0	349.0	352.0	30.0
Standard	14.0	12.4	12.4	13.0	12.4	11.1	11.3	11.0	9.0
error
IC of	[282.3;	[225.3;	[216.9;	[220;	[216.5;	[226.7;	[233.4;	[234.2;	[−78.3;
95%	338.3]	274.9]	266.4]	271.8]	266.1]	271.3]	278.8]	278.3]	−42.2]

Δ (%) em relação ao T0	−19.4

	Δ	Δ	Δ	Δ	Δ	Δ
	(T1 h −	(T2 h −	(T3 h −	(T4 h −	(T5 h −	(T6 h −
Subject	T0)	T0)	T0)	T0)	T0)	T0)
002	−77	−90	−75	−46	−46	−50
004	4	−39	−21	−4	−8	−25
005	−78	−67	−67	−67	−46	−60
006	−81	−73	−65	−75	−73	−81
007	−32	−37	4	−15	13	8
008	−41	−51	−50	−71	−68	−58
009	−103	−121	−132	−158	−106	−134
010	−6	34	8	28	−9	12
012	−81	−53	−76	−55	−14	−23
013	−65	−35	1	−35	−15	−12
014	−53	−63	−42	−73	−67	−39
015	−85	−89	−80	−24	−47	−42
016	−59	−7	−73	−94	−75	−61
017	−179	−146	−188	−140	−146	−137
018	−101	−63	−79	−96	−46	−41
019	−84	−110	−139	−45	−54	−63
020	−45	−82	−104	−60	−65	−61
021	−78	−85	−80	−65	−67	−75
022	−60	−46	−54	−70	−91	−85
Average	−68.6	−64.4	−69.1	−61.3	−54.2	−54.1
Medium	−77.0	−63.0	−73.0	−65.0	−54.0	−58.0
Minimum	−179.0	−146.0	−188.0	−158.0	−146.0	−137.0
Maximum	4.0	34.0	8.0	28.0	13.0	12.0
Standard	9.0	9.4	11.4	10.0	8.7	9.0
error
IC of	[−86.6;	[−83.1;	[−91.9; −46.2]	[−81.4; −41.3]	[−71.6;	[−72.1; −36]
95%	−50.6]	−45.7]			−36.8]
Δ (%) em relação	−22.1	−20.7	−22.3	−19.8	−17.5	−17.4
ao T0

TABLE 36
Average and standard error for each treatment per
time and for the difference between treatments

Product

Control

Product − Control

Time	Average	E.P.	Average	E.P.	Average	E.P.

T0	322.7	10.9	310.3	14.0	12.4	11.7
T30 min	247.6	13.2	250.1	12.4	−2.5	6.1
T1 h	236.0	12.9	241.7	12.4	−5.7	8.7
T2 h	239.4	12.0	245.9	13.0	−6.6	10.1
T3 h	234.6	12.5	241.3	12.4	−6.7	8.7
T4 h	245.8	10.9	249.0	11.1	−3.2	6.0
T5 h	257.2	10.5	256.1	11.3	1.1	6.7
T6 h	257.8	10.7	256.3	11.0	1.6	6.2

TABLE 37
Porcentage of variation in the average with respect to the T0
and percentage of volunteers with positive and negative effect

Produto − Controle

	% of
	variation with	% of subjects with	% of subjects with
Time	respect to T0	positive effect	negative effect

T30 min	−3.9	63.2	36.8
T1 h	−4.8	63.2	36.8
T2 h	−5.1	73.7	21.1
T3 h	−5.1	68.4	21.1
T4 h	−4.1	63.2	36.8
T5 h	−2.9	68.4	31.6
T6 h	−2.7	63.2	36.8

No significant difference was found between the treatments in the times T30min, T1h, T4h, T5h and T6h (P-values=0.138; 0.054; 0.147; 0.250; 0.207, respectively). The product was inferior to the control in the times T2h and T3h (p-values =0.048; 00.41, respectively).

Wherein:

Cm2: square centimeters;
G: grams;
H: hours;
No.: number;
° C.; degrees Celsius;
Tx: Time after x hours from application of the product.

6.7—Conclusion

• • After a statistical analysis of the results, one can conclude that the composition of the invention promoted the reduction of the erythema in the times T2h and T3h as compared with the control.